# Single cell analysis of the infiltrative margins of glioblastoma and post-treatment recurrence

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $348,948

## Abstract

Project Summary
Despite standard treatment with surgery, radiation and chemotherapy, glioblastomas (GBMs) inevitably recur
with fatal consequences. GBMs diffusely infiltrate the brain, making complete removal by surgical resection
impossible. The mixtures of neoplastic and non-neoplastic cells that remain in the infiltrated brain after surgical
debulking form the biological context for both adjuvant therapeutic intervention and recurrence. Furthermore,
radiation therapy, while beneficial for extending survival, may compromise the efficacy of targeted therapy and
induce treatment resistance. The goal of this study is to identify the molecular signatures in gliomas
responsible for recurrence and treatment resistance. Four innovative features will be incorporated: 1) a
methodology for radiographically -localized sampling of GBM and surrounding brain tissue; 2) new methods to
acquire and analyze Large-Scale Single Cell RNA-Seq data from mri-localized biopsies 3) a Ribotag mouse
model of GBM to experimentally track cell type-specific alterations associated with progression and recurrence.
In this proposal, tumor heterogeneity is approached from the perspective of CNS lineages, specifically looking
at the mixture of cell-types and the alterations in cell phenotypes that populate the tumor and surrounding
infiltrated brain tissue. Aim1 will determine the cellular and molecular composition of GBM at infiltrative margins
to demonstrate that glioma cells and reactive glia in the infiltrating margins differ from those in the tumor core.
We will also determine changes in cellular and molecular composition that occur between initial GBM resection
and post-treatment tumor recurrence. In Aim 2 we will use the RiboTag mouse model of proneural glioma to
determine if radiation induces mesenchymal transformation with a resultant resistance to targeted therapy. By
understanding the cellular and molecular composition of GBM and infiltrated brain tissue and comparing the
patterns of cell type-specific alterations that occur during glioma progression and following radiation therapy,
this proposal will reveal putative targets for glioma treatment and determine how specific glioma phenotypes
respond to current therapies.

## Key facts

- **NIH application ID:** 10202745
- **Project number:** 5R01NS103473-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** JEFFREY N BRUCE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $348,948
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202745

## Citation

> US National Institutes of Health, RePORTER application 10202745, Single cell analysis of the infiltrative margins of glioblastoma and post-treatment recurrence (5R01NS103473-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10202745. Licensed CC0.

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